Functional partitioning of transcriptional regulators by patterned charge blocks

Components of the transcriptional machinery are dynamically compartmentalized by weak multivalent interactions, yet we know little about how specificity or selectivity of partitioning is achieved. Here we show that condensates composed of the intrinsically disordered region (IDR) of MED1 (MED1_IDR) selectively partition positive regulators of transcription(SPT6, CTR9, IWS1) with RNA Pol II while excluding negative regulators of transcription (NELF and HP1a).This selective compartmentalization by MED1_IDR is sufficient to activate transcription and is required for gene activation during a cell state transition. Surprisingly, the IDRs of partitioned proteins are sufficient to recapitulate selective compartmentalization. We find that IDR-mediated selective partitioning requires multivalent blocks of positive and negative charge on MED1_IDR and IDRs of partitioned proteins. The charge patterns required for partitioning are also required for gene activation. These findings demonstrate that proteins can be functionally compartmentalized by specific multivalent interactions driven by the charge patterning within disordered regions. Overall design: Comparative gene expression profiling analysis of RNA-seq data for 3T3-L1 cells and mutants during adipocyte differentiation.